Post hoc Analysis of Edaravone Study 19: Efficacy in Bulbar Onset ALS Patients With and Without Reduced Pulmonary Function


Topic:

Clinical Trials

Poster Number: 53

Author(s):

Gary Pattee, MD, Gustavo Suarez Zambrano, Jeffrey Zhang, Sally Nelson, Stephen Apple, MD

Institutions:

1. Neurology Associates, P.C., 2. Mitsubishi Tanabe Pharma America, Inc., Jersey City, NJ, 3. Princeton Pharmatech, Princeton, NJ, 4. Mitsubishi Tanabe Pharma America, Inc., Jersey City, NJ, 5. Mitsubishi Tanabe Pharma America, Inc., Jersey City, NJ, USA

Background: In edaravone Study 19, patients with amyotrophic lateral sclerosis (ALS) experienced significantly less functional decline with edaravone vs placebo. In addition, a previous post hoc analysis of Study 19 revealed that ALS patients with reduced forced vital capacity (FVC) of <80% prior to starting edaravone, received a significant benefit after initiating treatment (33% difference; n=25). This study included both limb and bulbar-onset patients, therefore it was important to compare these groups regarding their response to edaravone treatment, and to assess bulbar patients with FVC ≥80% vs <80% at the time of treatment initiation.
Objective: To address the efficacy of edaravone in patients with bulbar-onset ALS and those bulbar patients with FVC of either ≥80% or <80%.
Approach: Post hoc analysis of Study 19 comparing edaravone efficacy in patients with bulbar vs limb-onset disease and FVC ≥80% vs <80%, as measured by ALS Functional Rating Score, Revised (ALSFRS-R).
Results: Following treatment, patients in both the bulbar and limb-onset groups experienced a reduction in ALSFRS-R score loss vs placebo patients through week 48. After starting edaravone, former placebo patients with either bulbar or limb-onset demonstrated a reduction in ALSFRS-R score loss from baseline to week 48, and a notable change in the slope of the ALSFRS-R score-vs-time graph. Analysis of bulbar-onset patients with either FVC ≥80% or <80% experienced a reduction in ALSFRS-R score loss vs placebo patients. In this report, no unexpected safety signals were seen, nor any inconsistencies with those of Study 19.
Conclusions: This analysis seems to indicate that ALS patients with bulbar-onset disease receive a significant benefit from initiating edaravone treatment regardless of whether they have baseline FVC ≥80% or <80%. The limitations inherent with post hoc analyses should be considered when interpreting these results.